In conclusion, this study has shown significant relationship between the rs4889 C/G polymorphisms in KISS1 gene and PCOS in Saudi females, where the mutant G allele is highly protective (OR = 0.294; 95% CI = 0.12–0.72, χ2 = 7.65; p = 0.006). This evidence concerns the gene KISS1 and polycystic ovary syndrome.